Does helping mothers in multigenerational ADHD also help children in the long run? 2-year follow-up from baseline of the AIMAC randomized controlled multicentre trial.

ADHD often affects multiple generations in a family. Previous studies suggested that children with ADHD benefit less from therapy if parents are also affected, since ADHD symptoms interfere with treatment implementation. This two-group randomised controlled trial examined whether targeting maternal ADHD boosts the efficacy of parent-child training (PCT) for the child's ADHD. Here, we report follow-up results 2 years from baseline. Mothers of 144 mother-child dyads (ADHD according to DSM-IV) were examined for eligibility (T1) and randomised to 12 weeks of intensive multimodal treatment comprising pharmacotherapy and DBT-based cognitive behavioural group psychotherapy (TG, n = 77) or clinical management comprising non-specific counselling (CG, n = 67) for Step 1 (concluded by T2). Subsequently, all dyads participated in 12 weekly PCT sessions for Step 2 (concluded by T3). In Step 3, participants received maintenance treatments for 6 months (concluded by T4). At 24 months after baseline (T5), we performed follow-up assessments. The primary endpoint was child ADHD/ODD score (observer blind rating). Outcomes at T5 were evaluated using ANCOVA. Assessments from 101 children and 95 mothers were available at T5. Adjusted means (m) of ADHD/ODD symptoms (range 0-26) in children did not differ between TG and CG (mean difference = 1.0; 95% CI 1.2-3.1). The maternal advantage of TG over CG on the CAARS-O:L ADHD index (range 0-36) disappeared at T5 (mean difference = 0.2; 95% CI - 2.3 to 2.6). Sensitivity analyses controlling for medication and significant predictors of follow-up participation showed unchanged outcomes. Within-group outcomes remained improved from baseline. At the 24-month follow-up, TG and CG converged. The superiority of intensive treatment regarding maternal symptoms disappeared. In general, cross-generational treatment seems to be effective in the long term. (BMBF grant 01GV0605; registration ISRCTN73911400).

Attention as neurocognitive endophenotype of ADHD across the life span: a family study.

Endophenotypes mediate pathways between genetic variations and the psychiatric phenotype, or share genetic risk with the psychiatric phenotype. Identifying endophenotypes is an important step to unravel disease pathways underlying complex psychiatric phenotypes such as ADHD. Potential viable endophenotypes for ADHD across the lifespan are neurocognitive measures of basic attention functions, such as sustained attention, and executive attention functions (EF), such as inhibition. The present study evaluated the endophenotype criteria of familiality and state-independency for measures of basic attention and EF in affected- and unaffected parents of children with ADHD (N = 139), and typically developing children (N = 60). In addition, the added value of neurocognitive measures relative to questionnaire data in genetically informed designs was explored by comparing the intergenerational transmission of neurocognitive measures to those of ADHD symptom scores. Results revealed small-to-medium-sized familial effects of ADHD for reaction time measures of EF components and state-independency given familial effects. Parent-child correlations as estimates of intergenerational transmission of those neurocognitive measures were not higher than those of behavioral ADHD symptom ratings. Taken together, our results argue against neurocognitive measures as pivotal endophenotypes for ADHD across the lifespan. If studied as neurocognitive endophenotypes of ADHD in adults, reaction time measures of executive-rather than basic attention function-seem to be more sensitive.

A multicentre randomized controlled trial on trans-generational attention deficit/hyperactivity disorder (ADHD) in mothers and children (AIMAC): an exploratory analysis of predictors and moderators of treatment outcome.

OBJECTIVE: We examined predictors and moderators of treatment outcome in mothers and children diagnosed with ADHD in a large multicentre RCT. METHOD: In total, 144 mother-child dyads with ADHD were randomly assigned to either a maternal ADHD treatment (group psychotherapy and open methylphenidate medication, TG) or to a control treatment (individual counselling without psycho- or pharmacotherapy, CG). After maternal ADHD treatment, parent-child training (PCT) for all mother-child dyads was added. The final analysis set was based on 123 dyads with completed primary outcome assessments (TG: n = 67, CG: n = 56). The primary outcome was the change in each child's externalizing symptoms. Multiple linear regression analyses were performed. RESULTS: The severity of the child's externalizing problem behaviour in the family at baseline predicted more externalizing symptoms in the child after PCT, independent of maternal treatment. When mothers had a comorbid depression, TG children showed more externalizing symptoms after PCT than CG children of depressive mothers. No differences between the treatment arms were seen in the mothers without comorbid depression. CONCLUSIONS: Severely impaired mothers with ADHD and depressive disorder are likely to need additional disorder-specific treatment for their comorbid psychiatric disorders to effectively transfer the contents of the PCT to the home situation (CCTISRCTN73911400).

Behavioral and psychological features in girls and women with triple-X syndrome.

Triple-X syndrome is a common sex chromosome aneuploidy, which appears in 1 out of 1,000 females. The aim of our study was to describe the behavioral features of a large group of girls and women with triple-X in comparison to a control group. A total of 72 subjects with triple-X and 69 subjects of an age-matched control group were included. Psychological and behavioral questionnaires were allocated to three age groups, representing a range of ages from young childhood to adulthood. Regarding the females between 4 and 7 years of age, we found significant differences for social problems, attention problems, and school performance. For the age group 8-17 years, we found larger significant differences for the majority of the scales listed in the child behavior checklist. The most significant differences (p < .001) were from total behavior problems, internalizing problems, and four other scales. Young females with triple-X have significantly lower general self-esteem, especially concerning school and family. In the adults, there were significant differences concerning psychological symptoms and distress, with higher scores in the triple-X subjects. Regardless, their mean scores were still in the normal range. We did not find clinical evidence for more than 50% of the triple-X females in any age group, indicating that approximately half of them do not have behavioral problems, and that more than 60% do not differ in their competence from the control group. However, our findings suggest that triple-X influences mental health and the overall well-being of the individuals across their whole life spans.

Attention profiles in autism spectrum disorder and subtypes of attention-deficit/hyperactivity disorder.

Attention problems are observed in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Most neuropsychological studies that compared both disorders focused on complex executive functions (EF), but missed to contrast basic attention functions, as well as ASD- and ADHD subtypes. The present study compared EF as well as basic attention functioning of children with the combined subtype (ADHD-C), the predominantly inattentive subtype (ADHD-I), and autism spectrum disorder without ADHD (ASD-) with typically developing controls (TD). Basic attention functions and EF profiles were analysed by testing the comprehensive attention function model of van Zomeren and Brouwer using profile analysis. Additionally, neurocognitive impairments in ASD- and ADHD were regressed on dimensional measures of attention- and hyperactive-impulsive symptoms across and within groups. ADHD-C revealed a strong impairment across measures of EF compared to ASD- and TD. The ADHD-C profile furthermore showed disorder specific impairments in interference control, whereas the ASD- profile showed a disorder specific impairment in basic attention component divided attention. Attention- and hyperactive-impulsive symptom severity did not predict neurocognitive impairments across- or within groups. Study findings thus support disorder and subtype specific attention/EF profiles, which refute the idea of a continuum of ADHD-I, ADHD-C, and ASD with increasing neurocognitive impairments.

Does the efficacy of parent-child training depend on maternal symptom improvement? Results from a randomized controlled trial on children and mothers both affected by attention-deficit/hyperactivity disorder (ADHD).

Multimodal treatment of children with ADHD often includes parent-child training (PCT). However, due to the high heritability, parents of children with ADHD are frequently also affected by the disorder, which is likely to constitute a significant barrier to successful treatment of the child. This secondary analysis of our randomized controlled multicentre AIMAC trial (ADHD in mothers and children) investigates whether children's outcomes following parent-child training in combination with maternal ADHD treatment depend on maternal symptom improvement. In a first step focusing on treatment of maternal ADHD, 144 mothers of mother-child dyads were randomized to multimodal ADHD treatment (group psychotherapy plus methylphenidate) or clinical management (mainly supportive counselling). After 12 weeks (T2), a 12-week PCT program (T2-T3) for all mother-child dyads was added to treat children's ADHD. Maternal symptomatology (CAARS-O:L; SCL-90-R) and children's externalizing symptoms (ADHD-ODD Scale, SDQ) were repeatedly assessed (T1 = baseline, T2, T3). Effects of changes in maternal symptomatology (T1-T2) on the change in children's symptom scores (T1-T3) were analysed using a general linear model, controlling for baseline scores, study centre, and maternal treatment group. 125 mother-child dyads were analysed. Mothers showed significant improvements in ADHD symptoms and overall psychopathology [CAARS-O:L ADHD index: mean - 3.54, SE 0.74 p < 0.0001; SCL-90-R Global Severity (GS): mean - 11.03, SE 3.90, p = 0.0056]. Although children's externalizing symptoms improved significantly (ADHD-ODD Scale: mean - 4.46, SE 0.58, p < 0.0001), maternal improvement had no effect on children's outcomes after Bonferroni-Holm correction for multiple testing. The findings do not support our hypothesis that children's outcomes following PCT for ADHD depend on maternal symptom improvements.Trial register CCT-ISRCTN73911400.

Group-based cognitive behavioural psychotherapy for children and adolescents with ASD: the randomized, multicentre, controlled SOSTA-net trial.

BACKGROUND: Group-based psychotherapy in Autism Spectrum Disorder (ASD) has predominantly been studied in the United States by small studies in school-aged children without long-term follow-up. We report results of a large, confirmatory, multicentre randomized-controlled phase-III trial in children and adolescents studying the ASD specific, manualized group-based cognitive behavioural SOSTA-FRA approach. METHODS: High-functioning ASD individuals aged 8-19 years old were randomized to 12 sessions SOSTA-FRA or treatment as usual. Primary outcomes were change in total raw score of the parent-rated Social Responsiveness Scale (pSRS) between baseline (T2) and end of intervention (T4), and between T2 and 3 months after end of intervention (T5). TRIAL REGISTRATION: ISRCTN94863788. RESULTS: Between 20/5/2010 and 14/2/2013, n = 320 ASD patients were screened, n = 228 patients were randomized, and N = 209 analysed. Mean pSRS difference between groups at T4 was -6.5 (95% CI -11.6 to - 1.4; p = .013), and at T5 -6.4 (-11.5 to -1.3, p = .015). Pre-treatment SRS and IQ were positively associated with stronger improvement at T4 and T5. CONCLUSIONS: Short-term ASD-specific add-on group-based psychotherapy has shown postintervention efficacy with regard to parent-rated social responsiveness predominantly in male high-functioning children and adolescents with ASD. Future studies should implement blinded standardized observational measures of peer-related social interaction.

Does intensive multimodal treatment for maternal ADHD improve the efficacy of parent training for children with ADHD? A randomized controlled multicenter trial.

BACKGROUND: This is the first randomized controlled multicenter trial to evaluate the effect of two treatments of maternal attention-deficit hyperactivity disorder (ADHD) on response to parent-child training targeting children's external psychopathology. METHODS: Mother-child dyads (n = 144; ADHD according to DSM-IV; children: 73.5% males, mean age 9.4 years) from five specialized university outpatient units in Germany were centrally randomized to multimodal maternal ADHD treatment [group psychotherapy plus open methylphenidate medication; treatment group (TG): n = 77] or to clinical management [supportive counseling without psychotherapy or psychopharmacotherapy; control group (CG): n = 67]. After 12 weeks, the maternal ADHD treatment was supplemented by individual parent-child training for all dyads. The primary outcome was a change in the children's externalizing symptom scores (investigator blinded to the treatment assignment) from baseline to the end of the parent-child training 6 months later. Maintenance therapy continued for another 6 months. An intention-to-treat analysis was performed within a linear regression model, controlling for baseline and center after multiple imputations of missing values. RESULTS: Exactly, 206 dyads were assessed for eligibility, 144 were randomized, and 143 were analyzed (TG: n = 77; CG: n = 66). After 6 months, no significant between-group differences were found in change scores for children's externalizing symptoms (adjusted mean TG-mean CG=1.1, 95% confidence interval -0.5-2.7; p = .1854), although maternal psychopathology improved more in the TG. Children's externalizing symptom scores improved from a mean of 14.8 at baseline to 11.4 (TG) and 10.3 (CG) after 6 months and to 10.8 (TG) and 10.1 (CG) after 1 year. No severe harms related to study treatments were found, but adverse events were more frequent in TG mothers than in CG mothers. CONCLUSIONS: The response in children's externalizing psychopathology did not differ between maternal treatment groups. However, multimodal treatment was associated with more improvement in maternal ADHD. Child and maternal treatment gains were stable (CCT-ISRCTN73911400).

Biological and psychosocial environmental risk factors influence symptom severity and psychiatric comorbidity in children with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a genetically as well as environmentally determined disorder with a high rate of psychiatric comorbidity. In this study, non-genetic biological and psychosocial risk factors for ADHD symptom severity and comorbid disorders were assessed in 275 children with ADHD, aged 5-13 years, mean age 9.7 (SD 1.9). Pre-/perinatal biological and lifetime psychosocial risk factors as well as data on parental ADHD were obtained. A different pattern of risk factors emerged for inattentive and hyperactive-impulsive ADHD symptoms. Inattentive symptoms were strongly influenced by psychosocial risk factors, whereas for hyperactive-impulsive symptoms, predominantly biological risk factors emerged. Hyperactive-impulsive symptoms also were a strong risk factor for comorbid oppositional defiant (ODD) and conduct disorder (CD). Smoking during pregnancy was a risk factor for comorbid CD but not ODD and further differential risk factors were observed for ODD and CD. Comorbid anxiety disorder (AnxD) was not related to ADHD symptoms and additional biological and psychosocial risk factors were observed. This study adds to the body of evidence that non-genetic biological and psychosocial risk factors have an impact on ADHD symptom severity and differentially influence comorbid disorders in ADHD. The findings are relevant to the prevention and treatment of ADHD with or without comorbid disorders.

Risk factors of autistic symptoms in children with ADHD.

Autistic symptoms are frequently observed in children with attention-deficit/hyperactivity disorder (ADHD), but their etiology remains unclear. The main aim of this study was to describe risk factors for increased autistic symptoms in children with ADHD without an autism or autism-spectrum diagnosis. Comorbid psychiatric disorders, developmental delay, current medication, prenatal biological and postnatal psychosocial risk factors as well as parental autistic traits were assessed in 205 children with ADHD. Linear regression models identified maternal autistic traits, current familial risk factors and hyperactive symptoms as predictors of autistic symptoms in children with ADHD. Findings are indicative of possible genetic as well as environmental risk factors mediating autistic symptoms in children with ADHD. An additional validity analysis by ROC, area under the curve (AUC), suggested a cut-off of 11 to differentiate between ADHD and high-functioning ASD by the Social Communication Questionnaire (SCQ).

Attention-deficit/hyperactivity disorder phenotype is influenced by a functional catechol-O-methyltransferase variant.

The catechol-O-methyltransferase gene (COMT) plays a crucial role in the metabolism of catecholamines in the frontal cortex. A single nucleotide polymorphism (Val(158)Met SNP, rs4680) leads to either methionine (Met) or valine (Val) at codon 158, resulting in a three- to fourfold reduction in COMT activity. The aim of the present study was to assess the COMT Val(158)Met SNP as a risk factor for attention-deficit/hyperactivity disorder (ADHD), ADHD symptom severity and co-morbid conduct disorder (CD) in 166 children with ADHD. The main finding of the present study is that the Met allele of the COMT Val(158)Met SNP was associated with ADHD and increased ADHD symptom severity. No association with co-morbid CD was observed. In addition, ADHD symptom severity and early adverse familial environment were positive predictors of lifetime CD. These findings support previous results implicating COMT in ADHD symptom severity and early adverse familial environment as risk factors for co-morbid CD, emphasizing the need for early intervention to prevent aggressive and maladaptive behavior progressing into CD, reducing the overall severity of the disease burden in children with ADHD.

Empirically Determined, Psychopathological Subtypes in Children With ADHD.

OBJECTIVE: The aim of this study was to empirically determine subgroups of ADHD defined by specific patterns of psychopathology. METHOD: A clinical sample of 223 children with ADHD, aged 5 to 14 years, was examined with the Child Behavior Checklist (CBCL). In addition, comorbid psychiatric disorders, psychosocial risk factors, and socioeconomic status were assessed. RESULTS: Cluster analysis of CBCL subscales yielded a solution with four distinct subgroups. While "externalizers" showed a high rate of comorbid oppositional defiant disorder (ODD) and conduct disorder (CD), "obsessive-compulsives" exhibited thought problems, low rates of comorbid CD, and high symptoms of inattention. "High psychiatric symptom carriers" had high rates of familial risk factors, acute life events, comorbid ODD, and CD. "Low psychiatric symptom carriers" also scored low in all other variables studied. CONCLUSION: Children with ADHD can be divided into four subgroups according to their CBCL-based psychopathology, and these subgroups differ in their risk factor profiles.

A randomized controlled multicentre trial on the treatment for ADHD in mothers and children: enrolment and basic characteristics of the study sample.

Parental ADHD may be a significant barrier to a successful treatment for the child's ADHD. The objective of our randomized controlled trial was to evaluate whether the treatment for maternal ADHD improves the efficacy of a behavioural parent training for children's ADHD. Patient enrolment and a description of the full analysis set (FAS) of mother-child pairs with non-missing baseline data are presented. One hundred and forty-four mother-child pairs were randomized to two treatments for maternal ADHD: cognitive behavioural group psychotherapy plus open methylphenidate treatment or control treatment (supportive counselling). After 3 months of treatment for maternal ADHD, mother-child pairs participated in a behavioural parent-child training. Assessment for eligibility included standardized instruments. After pre-screening out of 444 mother-child pairs, 206 were evaluated for trial participation and 144 were randomized. The FAS was built up by 143 dyads (children: mean age 9.4 years, 73 % males; mothers: mean age: 38.3 years). Fifty-two per cent of the children and 66 % of the mothers had combined ADHD subtype. Current axis-I co-morbidity rates were 48 % in children and 31 % in mothers. Maternal axis-II co-morbidity was 20.1 %. Fifty-seven per cent of the mothers lived together with the father of the index-child, and 29 % were single mothers. Sixty-two per cent had part-time or full-time employment. There was a selection bias excluding mothers with lack of time and effort for participation and mothers affected by coexisting mental and physical illness. Nevertheless, for our trial we were able to collect a sample comparable to routine psychiatric outpatient settings (registration: CCT-ISRCTN73911400, funding: BMBF-01GV0605).

Cortisol awakening response in healthy children and children with ADHD: impact of comorbid disorders and psychosocial risk factors.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common child psychiatric disorders. Previous studies have reported a blunted cortisol response to challenging situations and a decreased cortisol awakening response (CAR) in children with ADHD. As ADHD often is comorbid with oppositional defiant disorder (ODD), conduct disorder (CD), or anxiety disorder (AnxD), and changes in hypothalamic-pituitary-adrenal (HPA) axis activity have also been reported for these disorders, the present study aimed to compare the CAR in children with ADHD with and without comorbid disorders. Data on the CAR were obtained in 128 children with ADHD (aged 6-13 years) and in 96 control children (aged 6-12 years). Children with ADHD+ODD showed an attenuated CAR (area under the curve, AUC) compared to children with ADHD without ODD/CD and control children. Findings point towards either disinhibition or pervasive underarousal in children with ADHD+ODD, and seem to be specific for children with ADHD+ODD, as the attenuated CAR-AUC was not observed in children with ADHD without comorbid disorders or children with ADHD+CD or ADHD+AnxD. In addition, current adverse parenting conditions, family conflicts, and acute life events were associated with mean increase in CAR, emphasizing the role of psychosocial risk factors in mediating HPA axis activity in children with ADHD.